Seizure Activity in Alzheimer Disease: Levetiracetam May Help Detect Disease

High-frequency oscillation (HFO) patterns differ in Alzheimer disease (AD) and depend on epilepsy status, according to the findings of a study published in Brain Communications.

Hyperexcitability is a treatable contributor of cognitive decline, however, few biomarkers of hyperexcitability have been identified.

Researchers from the University of California, Los Angeles sourced data for this study from a phase 2A, randomized, crossover trial. Patients with AD (n=14) and control individuals (n=8) underwent magnetoencephalography (MEG) recordings with simultaneous electroencephalography (EEG) for 10 minutes starting at 40 minutes into a 60-minute resting-state examination. The patients underwent 4 and the control individuals 1 MEG and EEG (M/EEG) assessments. The patients with AD were randomly assigned to receive 125 mg levetiracetam twice a day or placebo for 4 weeks followed by a 4-week wash-out period and a 4-week crossover.

The patients with AD and epilepsy (EAD; n=8; mean age, 58.9; men, 62.5%), AD and without epilepsy (NEAD; n=6; mean age, 59.8; men, 33.3%), and control individuals (mean age, 71.1; men, 62.5%) were all White.

The correlations between ripples in 11 brain regions suggested independence in most brain regions (r range, -0.30 to 0.47).

Compared with control individuals, patients with AD had an increased ripple rate in 7 brain regions (mean range, 7.49-21.95vs 4.28-13.01 per hour; all P ≤.04) and fast ripple rate in 10 regions (mean range, 1.79-3.97 vs 0.84-1.84 per hour; all P ≤.036).

Stratified by epilepsy status, compared with control individuals, those with EAD had higher ripple rates in the left central and parietal regions and right occipital, parietal, and temporal regions (mean range, 7.07-21.95 vs 4.28-13.01 per hour; all P ≤.016) and NEAD in the left central, frontal, parietal, and temporal regions and right occipital, parietal, and temporal regions (mean range, 8.04-22.85 vs 4.28-13.01 per hour; all P ≤.008).

Fast ripple rates were higher in those with EAD in the left central and right occipital and temporal regions (mean range, 1.82-3.58 vs 0.84-4.47 per hour; all P ≤.0035) and NEAD in the left central, frontal, parietal, and temporal regions and right frontal, occipital, parietal, temporal regions and the cerebral fissure (mean range, 1.75-4.47 vs 0.84-1.84 per hour; all P ≤.022) than controls, respectively.

Among patients with AD, compared with EAD, NEAD associated with higher ripple rates in the left frontal and temporal and cerebral fissure regions (mean range, 14.38-19.00 vs 7.57-11.61; all P ≤.037) and fast ripple rates in the left frontal region (mean, 2.87 vs 1.64 per hour; P =.025).

Levetiracetam treatment decreased ripples in the left and right frontal and occipital and cerebral fissure regions in EAD (all P ≤.036) but increased ripples in the left and right parietal and right central regions in NEAD (all P ≤.0002). Levetiracetam also increased fast ripples in NEAD in the left parietal and right central regions (both P ≤.035).

“Alzheimer’s disease exhibited a higher rate of HFOs, with intriguing differences between NEAD and EAD. […] While HFOs can serve as a biomarker of hyperexcitability in Alzheimer’s disease, their role in Alzheimer’s disease pathology and progression requires further investigation,” the researchers concluded.